1-hydroxy-4, 7-methano-3a, 4, 7, 7a-tetrahydro 4, 5, 6, 7, 8, 8-hexachloroindene andmethod of preparing same



Patented Nov. 7, 1950 1-HYDRoxY-4,7 -METHANO 3a,4,7,7a-TETRA- HYDRO 4. 5. 6, 7, s. s HEXACHLOROINDENE AND METHOD or PREPARING SAME Simon H. Herzfeld and Eugene P. Ordas, Chicago, 111., assignors to Velsicol Corporation, Chicago, 111., a corporation of Illinois No Drawing. Application July 22, 1948,

Serial No. 40,156. 8 Claims. (01. 26i)617) This application is a continuation-in-part of our co-pendin application, Serial No. 735,526, filed March 18, 1947 now abandoned.

This invention relates to the production of new and useful compositions of matter.

More specifically, this invention is concerned with a new compositionof matter generally defined as the mono-hydrox derivative of the adduct of hexachlorocyclop-entadiene and cyclopentadiene, and to the method of production thereof. I

The Diels-Alder reaction of hexahalocyclopentadienes with cyclopentadiene has been disclosed in the co-pending application of Herzfeld, Lidov and Bluestone, Serial No. 581,172, filed March 5, 1945, and is symbolized as follows:

According to The Ring Index by Patterson and Capell, A. C. S. Monograph Series, No. 84,

1940, dicyclopentadiene, C10H12, is described as 4,7-methano-3a,4,7,7a-tetrahydroindene. Following this accepted system of nomenclature, the adduct of hexachlorocyclopentadiene and cyclopentadiene would be described as 4,7-methano- 3a,4,7,'7a tetrahydro 4,5,6,7,8,8 hexachloroindene. Hereinafter, for the purpose of brevity, this compound will be referred to as chlordene.

The compound with which this present invention is concerned is the l-hydroxy derivative of chlordene, which compound is a valuable intermediate in the preparation of insecticides and other new and valuable compositions. In accordance with the present invention, its method of preparation comprises formation of the l-bromo derivative of chlordene, which in turn is converted to the l-hydroxy derivative of chlordene by replacing the bromine constituent with an hydroxyl group.

The formation of l-bromo-chlordene is dependent upon the fact that in the presence of peroxides, bromine reacts with chlordene by substitution at the free methylene group. Small amounts of peroxides are normally contained in the reactants, but to insure a sufficient quantity it is preferable to add organic peroxides such as benzoyl peroxida-lauryl peroxide, or ascaridol, in the ratio of about 0.001 to 0.01 mol peroxide per mol of chlordene. -A. mol of bromine, orpreferably a slight excess thereof should be used'permol of chlordene, however, the ratio of these reactants can be-varied-over a very wide range and .any preference is based on economic rather than technical reasons. Bromination is accomplished by reacting liquid bromine, preferably contained in a relatively inert solvent such as carbon tetrachloride, chloroform, carbon disulfide, tetrachloroethylene or the like, with-chlordene contained in a solvent and in the presence of a peroxide as aforesaid. For effective reaction the bromine may be added tothe chlordene in the manner illustrated in the subsequent example. The time required for the reaction to proceed to completion, that is, when either or both of the reactants are completely used up, will depend on the concentration of reactants, temperature, agitation, and those other factors normally affecting reaction rates. It is not necessary that the reaction be completed, or that such reaction be terminated at completion, but large excesses of time should be avoided to minimize the formation of side products. The time when the reaction starts, the approximate rate ofreaction, and thetime when the reaction is completed can be estimated by the rate and'duration of time that hydrogen bromide isgenerated from the reaction mixture. The reaction will proceed to result in the formation of l-bromo-chlordene over fairly broad ranges o-fternperature, such as, for example, between about 15180 C. Reaction temperatures between about room temperature or slightly above "to about 120 C. are very satisfactory, and-good yields of product can be obtained at a reasonably rapid rate at temperatures of about to C. The reaction temperature can generally be adequately controlled by controlling the rate of introduction of bromine to the reaction mixture, however, external cooling or heating means can be utilized if desired. When the reaction is completed, or is otherwise abated after product is formed, the l-bromo-chlordene can be isolated by vacuum fractionation or any other method well known to the art. The reaction is almost quantitative, and yields of over based on he theoretical amount can be obtained.

The r p acement of the bromine atom in the l-bromo-chlordene with an hydroxyl group to form the desired l-hydroxy-chlordene, is accomplished directly by hydrolysis, either in an alkaline or an acid medium, or indirectly by the formation of an intermediate compound. which is then easi y converted to said hydroxy compound.

The alkaline aqueous hydrolysis is accomplished in the ordinary manner, such as, for example, by treating the l-bromo-chlordene with an aqueous solution of either a strongly alkaline material such as sodium h droxide or potassium hydroxide, or a weakly alkaline material such as sodium or potassium carbonate or bicarbonate, or calcium or barium hydroxide. The acid aqueous hydrolysis is also accomplished in the ordinary'manner, such as, for example, by treating the l-bromo-chlordene with an aqueous solution of a mineral acid such as sulfuric acid, p-toluene sul onic acid, hydrochloric acid, phosphoric acid,

with rapid a it tion for a period of from about one-half to about four days, depending upon such factors as alkalinity. t m erature and concentration of reactants. When reaction is over, the mono-hvdrox product c n be se arated and purified by filtration and r cry t lliz tion from a su t ble solvent. To enhance the rate of hydrolys s and to insure adequate re ction. it is pre erable that the re ction be effected'in the presen e of a solvent s ch as an alcohol, like pronanol. eth nol. or et ylene lycol or a solvent s ch as dioxane or the like. The rea tion time m y be con iderablv minimized by efi ectin hydrol sis at tem eratures some hat above 10 C. in homogeneous m xt res. The hi her tem erat res may be atta ned by using high boiling solvent or by carrying outthe reaction in an autoclave or by using both expedients. Excessively high temperatures such as will decompo e the reactants or product shoul be avoided. Thus, in general. tem ratures above about 60 C. are not desirable. The use of t mperatures m ch below' 100 C. is not desirable because t e rate of reaction is diminished. Since the reaction is one of hydroly is, t ere should be suflicient water pr s nt to hydrol ze the bromo com ound re erably sub tantially com letely. Where a solvent is utilized int e hydrolysis react on. it can be remo ed by ordinary means such as di tillat on at reduc d pressure if necessary. and the J-hfldl'OZY-ChlOl'dEl'lB can be recovered by filtration and recrystallization, or by any other known means.

An alternative method of conversion of lbromo-chlordene to 1-hydroxy-chlorflena is by indirect hydrolysis of l-bromo-chlordiene by esteri ying it to form t e acyloxy derivative of chlordene and subjecting the thereby formed l-acyloxy-chlordene to alcoholysis; said l-acyloxy-chlordene and method for preparings'ame being more particularlv described and claimed in our'co'oending a plication. Serial No. 40,155, filed July 22, 1948. The cblordene ester (l-acyloxychlordene) may be hydrolyzed to form l-hydroxychlordane in the manner that estersare normally hydrolyzed to result in an alcohol and an acid. However, the alcoholysis reaction is preferred in thisinstance because if hydrolysisbe used, it can be a plied directly to bromo-chlordene without the reparation of the intermediate acyloxy'compound- The formation of l-acyloxy chlordene ried out at the refl x temper ture of the mixture involves treating l-bromo-chlordene for from about one-half to about twenty hours or longer, depending on the nature and concentration of the reactants and the temperature employed, with the. salt of an organic: acid, such as the sodium, potassium or 'silver salt of acetic, propionic, butyric, benzoic acid, or the like, in the presence of a relatively inert solvent preferably capable of dissolving the reactants substantially completely, such as ethylene glycol, carbitol, propionic acid, dioxane, or preferably glacial acetic acid. Salts of organic acids having up to about twenty carbon atoms per molecule such as valeric, acrylic, butenoic, pentenoic, teracrylic, cinnamic, lauric, elaidic and others, may also be used to form l-acyloxychlcrdene: however. salts ofsaturated acids of a relatively low molecular weight, as aforementioned, are preferred in that they are more easily handled, and further, since the formation of an intermediate compound is involved, the use of the cheaper and more available salts is economical. The reaction temperature may vary within a fairly broad range, such as from about normal room temperature to about 170 (3., although it should not be so'low 'as. to cause the reaction to 'prccced at an inccnveniently slow rate nor so high as to decompose the reactants or the product. A satisfactory, though not necessarily limiting, temperature range is from about to about 150 C. It is convenient to carry out the reaction at the reflux temperature of the solvent employed thereby eliminating the necessity for'close temperature control. and thus, the use of a solvent boiling. at about C., such a acetic acid. is preferred. The ratio of reactants is not critical although a stoichiometric amount or an excess of the salt reactant is preferred to insure a maximum utilization of the bromo compound and conversion thereof to 1- acyloXy-c lordene. The amount of solvent utilized is also not critical. although a sufiiciency thereof to dissolve the reactants: and" the product is preferred. Large excesses of solvent should be avoided because of the dilution effect on the rate of the reaction. The solvent may be removed from thereaction product by distillation, at reduced pressures if necessary, and the residue, comprising the acyloxy derivative of chlordene can be either directly converted by alcoholysis or ester interchange reaction to the l-hydro ychlordene, or said residue may first be treated to obtain pure' l -acyloxy-chlordene. Purification may be accom lished b distillation in 'va uo'. by crystallization from suitable solvents, by preferential adsorption on porous materials, or by any other means known to the art.

The alcoholysis, or ester interchange reaction to convert l-acyloxy-chlordene to l-hydroxychlordene is carried out in the conventional manner (Fieser, L. F. and Fieser, M.,- Organic'Chemistry, 1944) by treating the ester with an alcohol or mixture of alcohols, preferably of arelatively low molecular weight, such as methanol, ethanol, propanol,- or ethylene glycol, which alcohols may act both as a solvent and a reactant in the presence of a proper catalyst, such as sulfuric or hydrochloric acid, or such basic compounds as sodium methoxide or sodium acetate. A relatively inert solvent in addition to the alcohol reactant may be utilized, but generally the use of such additional solvent is neither necessary nor preferred. The reaction temperature is that generally utilized in alcoholysis reactions. Thus, very low temperatures are not preferred because t ii Of. reaction is; then inordinately slow,

5. and temperatures above which decomposition of the reactants or product occurs should not be used. Generally temperatures within about 15 to about 160 C. are suitable, although not necessarily restrictive. and more specifically, temperatures between about 80 and 120 C. are preferred as resulting in a maximum yield within a reasonable time. Alcoholic reactants and solvents such as ethanol or propanol are preferred as the reaction may then be effected at the reflux temperatures of these solvents and the necessity for close temperature control is obviated. Under preferred temperature conditions, the reaction is initiated, and some product is formed in a very short period of time, namely, about fifteen minutes. The reaction is usually completed in about six hours, although the reaction may be maintained for longer periods inasmuch as excess reaction time is not deleterious to the product. The ratio of reactants is not critical and large excesses of alcohol may be utilized and even preferred. After reaction, the solvent may be removed by distillation, under reduced pressure if necessary, leaving a product comprising 1- hydroxy-chlordene which can be purified by distillation in vacuo, by crystallization, or by any other known means.

The following is a specific example of the method of our invention, for the purpose of i1" lustration.

Preparation of 1-bromo-chlordene A solution containing 1 mol (339 grams) chlordene and g. lauryl peroxide in 800 ml. carbon tetrachloride was placed into a 2-liter 3-necked flask eouipped with a reflux condenser, mechanical stirrer, thermometer and dropping funnel. This solution of chlordene was warmed to 50-55 C. and a bromine solution consisting of 176 grams bromine in 200 ml. carbon tetrachloride was introduced with a slow rate of stirring. The addition of the bromine solution was carried out at such rate as to maintain the temperature of the reaction vessel at 55 C. After addition was completed, the solution was refluxed for one-half hour to insure complete reaction. The reaction mixture was then washed with an excess of sodium bisulfite solution, washed with water, and dried in succession with calcium chloride and anhydrous magnesium sulfate. The solvent was re oved in vacuo and the residue distilled at 0.05 mm. ressure. The product thus obtained boiled at 130-132 C.

Analys s: Carbon, 27.64%: Hydrogen, 1.36%; Hal gen (as chlorine) 59.75%.

Calculated for C'oH5C1sBI1 Carbon, 28.74%; Hydrogen, 1.21%; Halogen (as chlorine) 59.40%.

The product is, therefore, l-bromo-chlordene.

Preparation of I-hydrozry-chlordene To a 2-liter, Z-necked flask was added 800 ml.

water, 200 ml. dioxane. 167.2 g. (0.4 mol) 1- bromo-chlordene, and 30.4 g. (0.22 mol) anhydrous potassium carbonate. The flask was equipped with a mechanical stirrer and reflux condenser, and the contents kept at refl x temperature with continuous, vigorous agitation for seventy-five hours. The reaction mixture was then diluted with three volumes of water and st rred until the organic phase solidified. The solid product was filtered, washed with water and dried first in air and then in an evacuated desiccator over potassium hydroxide. This crude product was recrystallized from hexane to yield a product melting at 197-200 C.

Analysis: Carbon, 34.07%; Hydrogen, 1.75%; Chlorine, 59.93%.

Calculated for CloHeClsO: Carbon, Hydrogen, 1.70%; Chlorine, 59.94%.

The product is therefore l-hydroxy-chlordene.

An alternative method for accomplishing the replacement of the bromine in l-bromo-chlordene by an hydroxyl group is as follows:

A mixture of 60 grams l-bromo-chlordene was refluxed with 35.4 grams anhydrous sodium acetate in 180 ml. glacial acetic acid for six hours. The solvent was distilled over to yield ml. of the glacial acetic acid used. The residue comprising l-acetoxy-chlordene was dissolved in benzene (200 ml.) and the extract was filtered. The solvent was then removed from the filtrate at reduced pressure, andthe l-acetoxy-chlordene was recrystallized from a benzene-petroleum ether mixture.

The thus purified l-acetoxy-chlordene was then dissolved in methanol using four grams of solvent per gram of residue. A small amount of concentrated hydrochloric acid (1.5 ml. per 60 grams of residue) was added to the solution and the material was refluxed for six hours. The

methanol was distilled over at reduced pressure and the residue purified by recrystallizat on from equal volumes of benzene and hexane. The purifled product thus obtained melted at l96-197 C. and resembled in all characteristics the compound obtained by the immediately previous method.

The position of the hydroxyl group introduced into the cl lordene molecule to result in the compound of the present invention is, as previously indicated b the numerical designation thereof and by the method of preparation, represented by the following structural formul and accompanying nomenclature:

1-hydroxy-4,7-n1ethano-3a.4.7.7a-tetrahydro- 4,5,6,7,8,8-hexachloroindene l-hyr roxy-chlo-rdene, the svnthesis of which is herein described is a new composition of matter which is useful as an insecticide, or as a starting or intermediate material in t e preparation of insecticides and other valuable classes of com ounds. Thus, the hydroxyl group may be replaced with a halogen atom to result in a very potent insecticide.

We claim as our invention:

1. As a new composition of matt r, l-hydroxy- 4,7 m t ano 3a,4,7,7a tetrahydro 4,5,6,7,8,8- hexachloroindene.

2. The method which comprises brominating 4,7 methano 3a,4,7,7a tetrahydro 4,5,6,7,8,8- hexachloroindene with bromine in the presence of a peroxide at a temperature between about 15 to about C. to form its l-bromo derivative, and re lacing the bromine substituent in said derivative with an hydroxyl group to form 1-hvdroxy-4.7-methano-3a,4,'7,7a-tetrahydro-4,5, 6,7,8,8-hexachloroindene.

3. The method of forming 1-hvdroxy-4,7- methano 3a,4,7,7a-tetrahvdro 4,5,6,7,8.8-hexachloroindene which comprises reacting 4,7- m t ano 3a,4,' .7a -tetrahvdro 4,5,6.7.8,8-hexa-v chlor-oindene with bromine in the presence of a peroxide at a temperature between about 15 to about 16.0? C;

amo ous;

about 18,0. C; to" form I-bromo.-4,'7 -methano.-3a, 4,7,7a -tetrahydro 4,5,6,'7,8,8 hexachloroindene;

and; hydrolyzingjsaid; li-bromo compound at a The method which comprises reacting. the

4,7 methano '-3a,4;7,7a tetrahydro 4,5',6,7,'8,8- hexach'loroindene. with: bromine in; the presence of a relatively inert solvent and an organic peroxidev at a temperature between about. room temperature to; about 120"" C.'. to: form the 1- bromo-4j7 -methano-3a,4,'7,'7a -tetrahydro-4,5;6,'7, 8,8:.-hexach1oroindene, and hydrolyzing" said 1- bromo: compound at atemperature between about 100 to about 160 C. to replace thev bromine: atom contained therein with an hydroxyl group;, I

- 6;The method which comprises reacting 4,7- methano- 3a,4,7,7a-tetrahydro 4,5,6,'7,8,8-hexachlorindene with bromine. in the presence of a peroxide to: form 1-bromo-4,7-methano-3a,4,7, '7a-tetrahydro-4;5,6;7,8,8 -hexachloroindene at a temperature between about room temperature amid- C. and hydrolyzing said l-bromo' compound with an aqueous alkaline reagent to produce l-hydroxy-4 ,'7-methano-3a,4;7,7a--tetrahydro-4,5;6i7;8,8-heXachloroindene.

8". 7-; They method which .compriseeyreaeting4;?- methano-3a-,41,'.'7,7a-,- tetrahydro --4,5, 6;7,8,8-hexa,-' chloroindenewith bromine in: the 7 presence of. a peroxide to form 1--bromo-4-,'7-methano-3a,4;7; 7a-tetrahydroA 5,6 7,8;8-hexach1oroindene at: a

temperature between about room temperatureand about 6., hydrolyzing said lebromo compound indirectlyby esterifying it and: subjecting' the thereby formed ester to alcoholysis at'a temperature between about 15: to a bout"' C to produce 1'-hydroxy -4;7-methano-3a4,7;7atetrahydrov-4,5,6',7,8,8-hexachloroindene;

'8.- The method which. comprises subjecting l-acy1oxy-4,7-methano 3a,4,7,7a-tetrahydro 4,5; 6,7;8,8-hexa'chlcroindene-to aicoho'lysis at a tern.- perature between about. 1-5 toabout 160 C. to form 1-hydr0Xy-4,-7methan0--3a,4;7,7a-tetrahydro-4,5,6.;7,8,8-hexach1oroindene.

SIMON- I-IJEIRZFELJ?- EUGENE' P. ORDAS.

REFERENCES CITED The following: references. are of record irrthe file of this patent:

UNITED. STATES PATENTS Number Name Date 2,278,527 Rust et a1. .cApr. 7 1942 2,318,033 Van. der Griendtet a1. May*4, 1943 OTHER, REFERENCES 

1. AS A NEW COMPOSTION OF MATTER, 1-HYDROXY4,7 - METHANO - 3A,4,7,7A-TETRAHYDRO-4,5,6,7,8,8HEXACHLOROINDENE. 